case report multiple brain metastases from nasopharyngeal carcinoma… · multiple brain metastases...

Int J Clin Exp Med 2016;9(11):22524-22530www.ijcem.com /ISSN:1940-5901/IJCEM0036191

Case ReportMultiple brain metastases from nasopharyngeal carcinoma: a case report and literatures review

Min Deng1, Yong Jiang2, Xiaojuan Zhou1, Xue Tian1, Youling Gong1

1Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China; 2Department of Pathology, West China Hospital, Sichuan Univer-sity, Chengdu 610041, PR China

Received July 19, 2016; Accepted September 15, 2016; Epub November 15, 2016; Published November 30, 2016

Abstract: Although direct intracranial invasion is common in patients with nasopharyngeal carcinoma (NPC), mul-tiple brain metastases from NPC is extremely rare. In this case, the clinical features, imaging, pathological find-ings, treatment outcomes, prognosis of an NPC patient with brain metastasis are described. Combining the clinical symptoms with auxiliary examination, the disease more likely to be originated from lung at first. Multiple biopsies confirmed that the primary lesions was nasopharynx finally. This is the first case of a patient with brain and lung metastasis from NPC that mimicked as a lung cancer. We also retrospectively reviewed the medical records of about 3200 patients with NPC treated in our hospital during 30 years and review relevant literatures from PUB-MED database. In summary, multiple brain metastases from NPC is extremely rare, and radiotherapy of brain lesions is an important auxiliary treatment besides the systematic therapy. The ultimate survival time depends on the effects from the chemotherapy and the control of extra-cranial disease.

Keywords: Nasopharyngeal carcinoma, multiple brain metastasis, lung metastasis, immunohistochemistry, treat-ment, prognosis

Introduction

Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia compared with Western coun-tries. During the past decade, the incidence of NPC is gradually declining, even in some endemic regions, and mortality from the dis-ease has fallen substantially [1]. Race, genet-ics, environment and Epstein-Barr virus (EBV) all play a role in the pathogenesis of NPC [2]. NPC has a propensity to cause distant metas-tasis; the most common sites of distant metas-tasis are the bone, lung and liver [3]. Maximizing the local control and minimizing the risk of dis-tant metastasis and late complications should be the main objectives in clinical work [4]. The presence of hepatic metastases, short metas-tasis free interval, and older age at presenta-tion significantly predicted short survival after the diagnosis of distant metastasis from NPC [5]. Because of nasopharyngeal anatomical location, NPC with direct extension to the brain is not rare, but true brain metastasis of NPC is exceedingly uncommon [6-9]. The prognosis of

NPC patients with brain metastasis is poor, which was depended on age, surgical excision and synchronous metastases, the survival gen-erally does not exceed 6 months [10]. Here, we reported a case of brain and lung metastasis from NPC which only appeared with the symp-toms of thoracic diseases.

Case report

A 49-year-old Chinese man was admitted to West China Hospital of Sichuan University, com-plaining of cough and expectoration for more than 1 months, and got deteriorated with accompanying bloody aputum and emptysis which was not alleviated with anti-inflammation treat-ment. The patient did not have epistaxis, rhino-stegnosis, facial numbness, diplopia, headache and vomit. None of positive signs were found upon physical examinations. Decreased breath-ing sound was found in his left lung.

Chest computed tomography (CT) showed soft tissues at the right hilum and left lower lobe

Multiple brain metastases from NPC: case report and literature review

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with enlarged hilum and mediastinum lymph nodes (Figure 1). The head magnetic resonance imaging (MRI) was performed, which showed multiple ring-enhancement lesions at left occipital lobe and bilateral parietal and frontal lobe (Figure 2). However, partial views of head MRI revealed incrassate tissue of right pharyn-geal recess. In order to define the position and scope of lesion, the nasopharyngeal MRI was perfomed. It showed right pharyngeal recess disappeared and was coveraged with soft tis-sue. Enlarged retropharyngeal space and cervi-cal lymph nodes also can be detected (Figure 3).

Bronchoscopy detected a strip of neoplasm at the orifice of the right middle bronchus. Imm- unohistochemical staining of tumor cells de- monstrated: CD5/6(+), P63(+), P40(+), CK7(-), TTF-1(-), ALK-V(-), ROS-1(-). The pharyngorhinos-copy and needle biopsy comfirmed its neo-plasmtic nature. The Immunohistochemical staining of tumor cells showed CK(-), P63(+), S- 100(-), Ki67(+, 40%) in situ hybridization EBE- R1/2(+), indicating it was the non-keratinizing carcinoma (Figure 4). Then the pathologist comfirmed EBER (partial +) in the tissue from the bronchoscopy. From these results, it can be concluded that the primary lesion was nasophar-

Figure 1. Chest computed tomography (CT) showed soft tissues at the right hilum (aboat 3.8 × 3.6 cm, A: Lung window, B: Mediastinum window) and left lower lobe (aboat 6.3 × 4.2 cm, C: Lung window, D: Mediastinum window) with enlarged hilum and mediastinum lymph nodes (E, F).


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ynx. Finally, The patient was diagnosed with nasopharyngeal non-keratinising squamous carci-noma accompanying with pharyngeal and mediastinum lymph nodes, bilateral lung, multiple brain metastases, T1N1M1b, stage IV [11].

Because that none of symtoms caused by brain metastasis was observed and the performance status of the patient was 2, the chemotherapy with Paclitaxel plus Cisplatin was performed after diagnosis, and the whole brain radiation

therapy (WBRT) was acheduled. During chemo-therapy process, the patient deteriorated with the thoracic symptoms rapidly and refused fur-ther anti-tumor treatment, only received best suppotive care, especially hemostatics. The patient finally died 4 months later from the diagnosis of NPC. He died of terminal massive hemoptysis and respiratory failure. Slight neu-rologic symptoms were observed, but no pro-gressive nasopharyngeal symptoms were observed before his demise.

Figure 2. Head magnetic resonance imaging (MRI) showed multiple ring-enhancement lesions at left occipital lobe and bilateral parietal and frontal lobe (arrows, A, B: Axial views; C-E: Sagittal views; F-I: Coronal views).


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Discussion

This is the first case reported a patient with brain and lung metastasis from NPC that mim-icked as the lung cancer at first, and multiple biopsies confirmed primary lesions was naso-pharynx finally. Sometimes, it is easy to misdi-agnose in practice. Missed diagnosis might cause the diseases deteriorated quickly or lead to other serious consequences. In clinical prac-tice, we should keep in mind the possibility of NPC brain and lung metastasis patient only

appeared with the symptoms of thoracic diseases.

In order to obtain more insight on incidence, clinical features, natural course, and treatment results of NPC with brain metastasis. We retro-spectively reviewed the medical records of about 3200 patients with nasopharyngeal car-cinoma treated in our hospital during 30 years (between 1985 and 2015). Patients with direct extension to the brain are excluded. Among them, 6 patients had been identified with brain

Figure 3. Nasopharyngeal magnetic resonance imaging (MRI) in (A, B) axial and (C) coronal views showed right pharyngeal recess disappeared and was coveraged with soft tissue. Enlarged retropharyngeal space and cervical lymph nodes also can be detected (arrows).

Figure 4. Photomicrographs of lung tumour cells (A-D) show (A) non-keratinising carcinoma (Haematoxylin & eosin, original magnification × 400), (B) Positive P63 staining in tumour cells (original magnification × 400), (C) positive Epstein-Barr virus-encoded RNA staining in tumour cells on in situ hybridisation (original magnification × 400) and (D) negative TTF-1 staining in tumour cells (original magnification × 400). Photomicrographs of nasopharyngeal tumour cells (E, F) show (E) non-keratinising carcinoma (Haematoxylin & eosin, original magnification × 400), (F) positive P63 staining in tumour cells (original magnification × 400) and (G) positive Epstein-Barr virus-encoded RNA staining in tumour cells on in situ hybridisation (original magnification × 400).


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Table 1. Brain metastasis from nasopharyngeal carcinoma in our hospital

Case Gender/age IT* Brain metastasis Metastasis† Treatment after brain metastasis Chemotherapy regime Treatment

response‡ ST§

1 Male/62 96 Multiple None WBRT, chemotherapy Cisplatin+5-Fu*4 SD 22 Male/48 24 Oligo Lung, bone BSC¶ None NA# 13 Male/59 84 Multiple None Surgery, WBRT, chemotherapy Paclitaxel+Cisplatin*6 SD 94 female/42 17 Multiple Lung, thyroid BSC None NA 15 Male/43 72 Single Lung, bone Gamma knife, chemotherapy Irinotecan+S-1*8 PR 46Present Male/49 0 Multiple Lung, Mediastinum Lymph nodes Chemotherapy+BSC Paclitaxel+Cisplatin*2 SD 4*Interval time between diagnosis of NPC and brain metastases in months; †Systemic metastasis at the time of brain metastasis diagnosis; ‡According to the RESIST criteria [12]; §Survival time after the diagnosis of brain metastases; #Not available; ¶Best supportive care.

Table 2. Brain metastasis from nasopharyngeal carcinoma from PUB-MED database

Case Gender/age IT* Brain metastasis Metastasis† Treatment after brain

metastasis Chemotherapy regime Treatment response‡ ST§

Liaw [6] Male/69 0 Multiple Bone WBRT+chemotherapy NA# NA# NANgan [7] Male/33 56 Single Cervical lymph nodes Surgery+chemotherapy Vincristine+5-Fu+Cyclophosphamide+Mthotrexate*2 PD 6Ozyar [9] Male/41 45 Single Lung Surgery+WBRT None SD NAOrit [8] Male/54 7 Single Petrous bone WBRT None PD NARafee [14] NA 7 Multiple Lung WBRT+chemotherapy Carboplatin+5-FU*4 PR NA*Interval time between diagnosis of NPC and brain metastases in months; †Systemic metastasis at the time of brain metastasis diagnosis; ‡According to the RESIST criteria [12]; §Survival time after the diagnosis of brain metastases; #Not available.


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metastasis. Their information is shown in Table 1. We evaluate the treatment response accord-ing to the RESIST criteria [12]. SPSS statistical software (version 19.0) was used to calculate median time and corresponding 95% confi-dence intervals (CIs).

The interval time between the diagnosis of NPC and brain metastases is among 0-96.0 months, and the median interval time of all patients is 48 months (95% CI 20.5-76.0 months). The patients’ survival time after brain metastasis is among 1.0-46.0 months, the median survival time is about 3.0 months (95% CI 1.7 -25.2 months). Among them, two patients’ perfor-mance status worsened rapidly after they had brain metastases. Both of them were accom-panied by disease recurrences in multiple sites and lost in our follow-up.

It’s worth mentioning that one patient’s surviv-al time after brain metastasis is 46 months. This patient had lung metastasis and progres-sive nasopharyngeal lesion 64 mouths after the diagnosis of NPC. We treated him with che-motherapy of Docetaxel and Oxaliplatin. How- ever, a new cerebellum metastasis (about 1.1*1.7 cm) was observed after 8 months from the diagnosis of lung metastasis. It has been concluded that in patients with a single or less than three, small sized brain metastasis, Gamma knife treatment was less invasive, and it could control local tumor as effectively as surgery plus postoperative whole brain irradia-tion (WBRT) in a randomized controlled multi-centre phase III trial [13]. So, the patient had received Gamma-knife therapy. In order to con-trol the systematic metastasis of NPC, we treated the patient with multi-line chemothera-py, including Taxol plus Oxaliplatin, Vinorelbine plus Cisplatine, Etoposide alone after his dis-ease progression each time. Finally, the tho-racic disease became refractory, and the patient died after 46 months from the diagno-sis of brain metastasis. The symptoms of brain and nasopharyngeal didn’t worsen before he died.

Furthermore, we conducted a systematic se- arch in the PUB-MED databases to identify all reports that contained nasopharyngeal carci-noma with brain metastases. Only 5 reports are identified, as shown in Table 2. The interval time between the diagnosis of NPC and brain metastases is among 0.0-56.0 months, and

the median interval time of these patients is 7 months (95% CI 4.2-44.0 months).

Only Ngan et al [7] recorded the patient’s sur-vival time after the diagnosis of brain metasta-sis, it was 6.0 months. This patient had left occipital lobe metastasis after 2 cycles chemo-therapy consisting of vincristine, 5-fluorouracil, cyclophosphamide, and methotrexate which was used to control the lung metastases. Then a neuro-surgery was performed to remove the brain tumor. However, the thoracic disease pro-gressed gradually after the craniotomy. The patient died 6 months later from the diagnosis of brain metastasis. The authors believed that no matter radiotherapy or not, patients with CNS metastasis can achieve good symptom and disease control after surgery, and the ulti-mate survival depends on the control of extra- cranial disease after aggressive therapy.

Rafee et al [14] presented a patient achieving good response to the treatment. This patient had leptomeningeal disease and multiple brain metastasis eight months after treatment of pri-mary NPC. Palliative radiotherapy was adminis-tered to the spine and brain, and palliative che-motherapy with Carboplatin and 5-FU infusion every three weeks, with Cetuximab weekly and intrathecal Cytarabine infusion every two weeks. After six cycles of treatment, MRI revealed a significant improvement with near resolution of intracranial metastases.

For the first time, we reported a patient with multiple brain and lung metastases from NPC who was admitted with pulmonary symptoms. The lung metatases of this patient were not multiple small nodular lesions in peripheral pul-monary. There were massive lesions in bilateral hilus, so the symptoms of bloody aputum and emptysis were abserved at first. As we know, platinum-based chemotherapy is the recom-mended as the first-line treatment for meta-static NPC, but no standard treatment regi-mens have been established. Chen et al [15] reported a triplet combination chemotherapy with paclitaxel, cisplatin and 5-FU was an effec-tive and safe option to improve the response rate and prolong OS among these pateints. However, Jin et al [16] considered that the three-drug combined regimens brought more toxicity without survival benefits, cisplatin-based doublets may be the more appropriate choice as the first-line treatment for patients


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with metastatic NPC. The platinum-based dou-blet regimens also could achieve the response rates of 70-80% [1]. Because the performance score of this patient was 2 and accompanied with obvious emptysis, we considered the patient might not tolerate a triplet combination chemotherapy and choosed TP regimen (Paclitaxel and Cisplatin). During chemotherapy process, the patient deteriorated with the tho-racic symptoms rapidly and died of terminal massive hemoptysis and respiratory failure finally.

Conclusion

Based on literatures review, it could be con-cluded that multiple brain metastases from NPC is extremely rare. Systematic therapy is the main treatment method, and radiotherapy of brain lesions is an important auxiliary treat-ment method. The prognosis of NPC patients with brain metastasis is poor. The ultimate sur-vival time depends on the reaction to chemo-therapy and the control of extra-cranial disease.

Disclosure of conflict of interest

None.

Address correspondence to: Dr. Youling Gong, De- partment of Thoracic Oncology and State Key La- boratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Number 37, Guoxue Alley, Chengdu 610041, Sichuan, PR China. Tel: 86-28-85423581; Fax: 86-28-85423571; E-mail: [email protected]

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[8] Kaidar-Person O, Kuten J, Atrash F, Billan S, Kuten A. Brain metastasis of nasopharyngeal carcinoma: a case report and literature review. Case Rep Med 2012; 2012: 405917.

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case report multiple brain metastases from nasopharyngeal carcinoma… · multiple brain metastases...

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